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Clinical pharmacology of carvedilol in normal volunteers
Insights
Carvedilol effectively lowers blood pressure by blocking alpha-1 and beta-receptors, demonstrating greater potency than labetalol in this vasodilatory action.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
Background:
- Carvedilol is a novel antihypertensive agent.
- Understanding its vasodilatory mechanism is crucial for clinical application.
Purpose of the Study:
- To investigate the vasodilatory mechanism of carvedilol.
- To compare its efficacy and potency against labetalol.
Main Methods:
- Continuous monitoring of intra-arterial blood pressure and ECG in normal volunteers.
- Administration of carvedilol and labetalol infusions.
- Assessment of responses to isoproterenol and phenylephrine challenges.
Main Results:
- Carvedilol significantly reduced blood pressure (23% systolic, 18% diastolic) with transient heart rate increase.
- Carvedilol demonstrated greater hypotensive effects than labetalol at comparable doses.
- Both drugs antagonized isoproterenol and phenylephrine effects, with carvedilol showing higher potency.
Conclusions:
- Carvedilol exhibits both alpha-1 and nonselective beta-receptor blocking properties.
- Carvedilol is 3-5 times more potent than labetalol in receptor blockade and blood pressure reduction.
Abstract:
The mechanism of the vasodilatory action of carvedilol (BM 14190), a new antihypertensive agent, was investigated in normal volunteers. Intra-arterial blood pressure and ECG were monitored continuously. Carvedilol (1 mg/min for 15 minutes) produced a rapid reduction in blood pressure and a transient increase in heart rate. At the end of infusion, systolic and diastolic blood pressure were reduced by 23% (-32.3 mm Hg) and 18% (-13.6 mm Hg), respectively, whereas heart rate was not different from baseline. At the doses used, the hypotensive effect of carvedilol was greater than that of labetalol (36 and 72 mg in 15 minutes). Carvedilol and labetalol antagonized isoproterenol-induced hypotension and tachycardia, at serum levels greater than or equal to 8 and 20 mg/ml, respectively. Both drugs antagonized phenylephrine pressor effects. A similar degree of inhibition (25% of control) of pressor effects was observed for carvedilol and labetalol when their respective serum concentrations were 23 ng/ml and 80 ng/ml. Neither carvedilol nor labetalol had any effect on AII pressor responses. Carvedilol serum levels as high as 150 ng/ml failed to inhibit AII-induced pressor responses. Our results suggest that at the doses used in this study, carvedilol has both alpha 1-and nonselective beta-receptor blocking properties. Moreover, carvedilol is approximately three to five times more potent than labetalol in blocking alpha 1-and beta-receptors and in reducing blood pressure.